FOXA1

Forkhead box A1
Identifiers
Symbols	FOXA1 ; HNF3A; TCF3A
External IDs	OMIM: 602294 MGI: 1347472 HomoloGene: 3307 GeneCards: FOXA1 Gene
Gene ontology Molecular function • RNA polymerase II transcription factor activity, sequence-specific DNA binding • transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding • DNA binding • transcription factor activity, sequence-specific DNA binding • transcription factor binding • protein domain specific binding • sequence-specific DNA binding • transcription regulatory region DNA binding Cellular component • nucleus • nucleolus • microvillus Biological process • chromatin remodeling • transcription from RNA polymerase II promoter • anatomical structure morphogenesis • negative regulation of epithelial to mesenchymal transition • dorsal/ventral neural tube patterning • cell differentiation • response to estradiol • positive regulation of intracellular estrogen receptor signaling pathway • hormone metabolic process • glucose homeostasis • positive regulation of neuron differentiation • positive regulation of smoothened signaling pathway • positive regulation of mitotic cell cycle • positive regulation of transcription from RNA polymerase II promoter • anatomical structure formation involved in morphogenesis • neuron fate specification • positive regulation of sequence-specific DNA binding transcription factor activity • epithelial tube branching involved in lung morphogenesis • lung epithelial cell differentiation • secretory columnal luminar epithelial cell differentiation involved in prostate glandular acinus development • epithelial-mesenchymal signaling involved in prostate gland development • prostate gland epithelium morphogenesis • prostate gland stromal morphogenesis • epithelial cell maturation involved in prostate gland development • positive regulation of cell-cell adhesion mediated by cadherin Sources: Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	3169	15375
Ensembl	ENSG00000129514	ENSMUSG00000035451
UniProt	P55317	P35582
RefSeq (mRNA)	NM_004496	NM_008259
RefSeq (protein)	NP_004487	NP_032285
Location (UCSC)	Chr 14: 37.59 – 37.6 Mb	Chr 12: 57.54 – 57.55 Mb
PubMed search

Forkhead box protein A1 (FOXA1), also known as hepatocyte nuclear factor 3-alpha (HNF-3A), is a protein that in humans is encoded by the FOXA1 gene.^[1][2][3]

Function

FOXA1 is a member of the forkhead class of DNA-binding proteins. These hepatocyte nuclear factors are transcriptional activators for liver-specific transcripts such as albumin and transthyretin, and they also interact with chromatin as a pioneer factor. Similar family members in mice have roles in the regulation of metabolism and in the differentiation of the pancreas and liver.^[1]

Marker in breast cancer

FOXA1 in breast cancer is highly correlated with ERα⁺, GATA3⁺, and PR⁺ protein expression as well as endocrine signaling. FOXA1 acts as a pioneer factor for ERa in ERα⁺ breast cancer, and its expression might identify ERα⁺ cancers that undergo rapid reprogramming of ERa signaling that is associated with poor outcomes and treatment resistance.^[4] Conversely, in ERα⁻ breast cancer FOXA1 is highly correlated with low-grade morphology and improved disease free survival. FOXA1 is a downstream target of GATA3 in the mammary gland.^[5] Expression in ERα⁻ cancers may identify a subset of tumors that is responsive to other endocrine therapies such as androgen receptor antagonist treatment.^[6][7]

Role in prostate cancer

Mutations in this gene have been recurrently seen in instances of prostate cancer.^[8]

References

1. "Entrez Gene: forkhead box A1".
2. Bingle CD, Gowan S (1996). "Molecular cloning of the forkhead transcription factor HNF-3 alpha from a human pulmonary adenocarcinoma cell line.". Biochim Biophys Acta 1307 (1): 17–20. doi:10.1016/0167-4781(96)00058-9. PMID 8652662.
3. Mincheva A, Lichter P, Schütz G, Kaestner KH (1997). "Assignment of the human genes for hepatocyte nuclear factor 3-alpha, -beta, and -gamma (HNF3A, HNF3B, HNF3G) to 14q12-q13, 20p11, and 19q13.2-q13.4.". Genomics 39 (3): 417–9. doi:10.1006/geno.1996.4477. PMID 9119385.
4. Ross-Innes, Caryn S.; Stark, Rory; Teschendorff, Andrew E.; Holmes, Kelly A.; Ali, H. Raza; Dunning, Mark J.; Brown, Gordon D.; Gojis, Ondrej; Ellis, Ian O.; Green, Andrew R.; Ali, Simak; Chin, Suet-Feung; Palmieri, Carlo; Caldas, Carlos; Carroll, Jason S. (4 January 2012). "Differential oestrogen receptor binding is associated with clinical outcome in breast cancer". Nature 481 (7381): 389–93. doi:10.1038/nature10730. PMC 3272464. PMID 22217937. Cite uses deprecated parameter |coauthors= (help)
5. Kouros-Mehr H, Slorach EM, Sternlicht MD, Werb Z (December 2006). "GATA-3 maintains the differentiation of the luminal cell fate in the mammary gland". Cell 127 (5): 1041–55. doi:10.1016/j.cell.2006.09.048. PMC 2646406. PMID 17129787.
6. Albergaria A, Paredes J, Sousa B, Milanezi F, Carneiro V, Bastos J, Costa S, Vieira D, Lopes N, Lam EW, Lunet N, Schmitt F (2009). "Expression of FOXA1 and GATA-3 in breast cancer: The prognostic significance in hormone receptor-negative tumours". Breast Cancer Research 11 (3): R40. doi:10.1186/bcr2327. PMC 2716509. PMID 19549328.
7. Sanga S, Broom BM, Cristini V, Edgerton ME (2009). "Gene expression meta-analysis supports existence of molecular apocrine breast cancer with a role for androgen receptor and implies interactions with ErbB family". BMC Medical Genomics 2: 59. doi:10.1186/1755-8794-2-59. PMC 2753593. PMID 19747394.
8. Barbieri CE, Baca SC, Lawrence MS, Demichelis F, Blattner M, Theurillat JP, White TA, Stojanov P, Van Allen E, Stransky N, Nickerson E, Chae SS, Boysen G, Auclair D, Onofrio RC, Park K, Kitabayashi N, MacDonald TY, Sheikh K, Vuong T, Guiducci C, Cibulskis K, Sivachenko A, Carter SL, Saksena G, Voet D, Hussain WM, Ramos AH, Winckler W, Redman MC, Ardlie K, Tewari AK, Mosquera JM, Rupp N, Wild PJ, Moch H, Morrissey C, Nelson PS, Kantoff PW, Gabriel SB, Golub TR, Meyerson M, Lander ES, Getz G, Rubin MA, Garraway LA (June 2012). "Exome sequencing identifies recurrent SPOP, FOXA1 and MED12 mutations in prostate cancer". Nat. Genet. 44 (6): 685–9. doi:10.1038/ng.2279. PMC 3673022. PMID 22610119.

Further reading

• Song L, Xu Z, Zhang C; et al. (2009). "Up-regulation of the HSP72 by Foxa1 in MCF-7 human breast cancer cell line.". Biochem. Biophys. Res. Commun. 386 (1): 30–4. doi:10.1016/j.bbrc.2009.05.120. PMID 19486887.
• Zhang Y, Ali TZ, Zhou H; et al. (2010). "ErbB3 binding protein 1 represses metastasis-promoting gene anterior gradient protein 2 in prostate cancer.". Cancer Res. 70 (1): 240–8. doi:10.1158/0008-5472.CAN-09-2904. PMID 20048076.
• McMullin RP, Dobi A, Mutton LN; et al. (2010). "A FOXA1-binding enhancer regulates Hoxb13 expression in the prostate gland.". Proc. Natl. Acad. Sci. U.S.A. 107 (1): 98–103. doi:10.1073/pnas.0902001107. PMC 2806740. PMID 20018680.
• Sun Q, Yu X, Degraff DJ, Matusik RJ (2009). "Upstream stimulatory factor 2, a novel FoxA1-interacting protein, is involved in prostate-specific gene expression.". Mol. Endocrinol. 23 (12): 2038–47. doi:10.1210/me.2009-0092. PMC 2796152. PMID 19846536.
• Liu N, Niu Y, Wang SL; et al. (2010). "[Diagnostic and prognostic significance of FOXA1 expression in molecular subtypes of breast invasive ductal carcinomas]". Zhonghua Yi Xue Za Zhi 90 (20): 1403–7. PMID 20646630.
• Haiman CA, Garcia RR, Hsu C; et al. (2009). "Screening and association testing of common coding variation in steroid hormone receptor co-activator and co-repressor genes in relation to breast cancer risk: the Multiethnic Cohort.". BMC Cancer 9: 43. doi:10.1186/1471-2407-9-43. PMC 2637888. PMID 19183483.
• Kohler S, Cirillo LA (2010). "Stable chromatin binding prevents FoxA acetylation, preserving FoxA chromatin remodeling.". J. Biol. Chem. 285 (1): 464–72. doi:10.1074/jbc.M109.063149. PMC 2804194. PMID 19897491.
• Malik S, Jiang S, Garee JP; et al. (2010). "Histone deacetylase 7 and FoxA1 in estrogen-mediated repression of RPRM.". Mol. Cell. Biol. 30 (2): 399–412. doi:10.1128/MCB.00907-09. PMC 2798473. PMID 19917725.
• Motallebipour M, Ameur A, Reddy Bysani MS; et al. (2009). "Differential binding and co-binding pattern of FOXA1 and FOXA3 and their relation to H3K4me3 in HepG2 cells revealed by ChIP-seq.". Genome Biol. 10 (11): R129. doi:10.1186/gb-2009-10-11-r129. PMC 3091322. PMID 19919681.
• Eeckhoute J, Lupien M, Meyer CA; et al. (2009). "Cell-type selective chromatin remodeling defines the active subset of FOXA1-bound enhancers.". Genome Res. 19 (3): 372–80. doi:10.1101/gr.084582.108. PMC 2661808. PMID 19129543.
• Nakshatri H, Badve S (2007). "FOXA1 as a therapeutic target for breast cancer.". Expert Opin. Ther. Targets 11 (4): 507–14. doi:10.1517/14728222.11.4.507. PMID 17373880.
• Iacobazzi V, Infantino V, Bisaccia F; et al. (2009). "Role of FOXA in mitochondrial citrate carrier gene expression and insulin secretion.". Biochem. Biophys. Res. Commun. 385 (2): 220–4. doi:10.1016/j.bbrc.2009.05.030. PMID 19445897.
• Nucera C, Eeckhoute J, Finn S; et al. (2009). "FOXA1 is a potential oncogene in anaplastic thyroid carcinoma.". Clin. Cancer Res. 15 (11): 3680–9. doi:10.1158/1078-0432.CCR-08-3155. PMID 19470727.
• Nakshatri H, Badve S (2009). "FOXA1 in breast cancer.". Expert Rev Mol Med 11: e8. doi:10.1017/S1462399409001008. PMID 19261198.
• Song Y, Washington MK, Crawford HC (2010). "Loss of FOXA1/2 is essential for the epithelial-to-mesenchymal transition in pancreatic cancer.". Cancer Res. 70 (5): 2115–25. doi:10.1158/0008-5472.CAN-09-2979. PMC 2831111. PMID 20160041.
• Lee HJ, Chattopadhyay S, Yoon WH; et al. (2010). "Overexpression of hepatocyte nuclear factor-3alpha induces apoptosis through the upregulation and accumulation of cytoplasmic p53 in prostate cancer cells.". Prostate 70 (4): 353–61. doi:10.1002/pros.21069. PMID 19866472.
• Bernardo GM, Lozada KL, Miedler JD; et al. (2010). "FOXA1 is an essential determinant of ERalpha expression and mammary ductal morphogenesis.". Development 137 (12): 2045–54. doi:10.1242/dev.043299. PMC 2875844. PMID 20501593.
• Albergaria A, Paredes J, Sousa B; et al. (2009). "Expression of FOXA1 and GATA-3 in breast cancer: the prognostic significance in hormone receptor-negative tumours.". Breast Cancer Res. 11 (3): R40. doi:10.1186/bcr2327. PMC 2716509. PMID 19549328.
• Huang QY, Li GH, Kung AW (2009). "The -9247 T/C polymorphism in the SOST upstream regulatory region that potentially affects C/EBPalpha and FOXA1 binding is associated with osteoporosis.". Bone 45 (2): 289–94. doi:10.1016/j.bone.2009.03.676. PMID 19371798.
• Sano M, Aoyagi K, Takahashi H; et al. (2010). "Forkhead box A1 transcriptional pathway in KRT7-expressing esophageal squamous cell carcinomas with extensive lymph node metastasis.". Int. J. Oncol. 36 (2): 321–30. doi:10.3892/ijo_00000503. PMID 20043065.

External links

• FactorBook FOXA1

This article incorporates text from the United States National Library of Medicine, which is in the public domain.